Lec6 Adrenal cortex: Hormones & Physiology Flashcards
Anatomy of adrenal cortex Synthesis and actions of glucocorticoids Synthesis and actions of mineralocorticoids Therapeutic uses of corticosteroids
What percentage of the adrenal gland is cortex?
90%
What percentage of the adrenal gland is the inner medulla?
10%
What is the function of the medulla?
Neuroendocrine tissue which secretes catecholamines and is responsible for the stress response
What is the function of the adrenal cortex?
Involved in salt, glucose and stress homeostasis
Which out of the two: functioning adrenal medulla or functioning adrenal cortex is essential for life?
Adrenal cortex
What type of hormones does the adrenal cortex synthesise?
Steroid hormones - all with similar chemical structure
What molecule are the steroid hormones derived from and where does this molecule come from?
Steroid hormones are synthesised from cholesterol
Cholesterol comes from the diet or is synthesised within the gland itself
What are the three layers of the adrenal cortex and what do they synthesise?
Outer zona glomerulosa
Middle zona fasciculata
Inner zona reticularis
They synthesise adrenocortical steroid hormones
How do the cells within these three layers produce different steroid hormones?
because they possess different enzymes which produce different steroid hormones with a variety of effects
How are steroid hormones classified?
according to their predominant action
What are the major secretions of the adrenal cortex?
Glucocorticoids e.g. cortisol
Mineralocorticoids e.g. aldosterone
What is the function of glucocorticoids?
To control blood glucose
What is the function of mineralocorticoids?
To control sodium and potassium concentrations
What is the Synthetic pathway?
The synthetic pathway is all the steps which leads from cholesterol to becoming aldosterone, cortisol and testosterone
Which enzyme does the zona glomerulosa have?
18-hydroxylase enzyme - leading to aldosterone synthesis
Which enzyme does the zona fasciculata and zona reticularis have?
17alpha hydroxylase
Therefore 17alpha-hydroxypregnenolone and 17alpha-hydroxyprogesteron and the hormones derived from them are synthesised
i.e. cortisol and androgens (testosterone)
Where is cortisol synthesised?
Zona fasciculata
Where are androgens synthesised?
Zona reticularis
Under normal circumstances, what does the adrenal cortex secrete in small quantities?
Androgens i.e. dehydroepiandrosterone, androstenedione and testosterone and female oestrogens e.g. oestrodiol
When does the secretion of testosterone from the adrenal cortices increase?
Only in adrenal disorders, when things go wrong otherwise testosterone is secreted in very small amounts
Describe the control of cortisol secretion
The hypothalamus secreted corticotrophin releasing hormone (CRH) which acts on the pituitary gland to secrete adrenocorticotrophic hormone (ACTH). ACTH acts on the adrenal cortex to secrete cortisol
Cortisol has a negative feedback loop preventing further release of CRH from the hypothalamus
Describe the secretion pattern of ACTH
ACTH secretion is pulsatile
Peak ACTH very early in the morning
Nadir in the middle of the night
When does increased secretion of ACTH occur?
During prolonged periods of stress
Describe the secretion pattern of cortisol
Secretion of cortisol is also pulsatile
But the peak and nadir are about 2 hours after those of ACTH
What does the pattern of ACTH and cortisol secretion relate to and when is this disturbed?
Sleep-wake cycles
Disturbed by shift work and long haul travel
Jet lag caused by a perturbation to the diurnal rhythm of ACTH and cortisol
What percentage of cortisol is free/ unbound?
10%
What are the proteins that cortisol is bound to and in what percentages?
Corticosteroid binding globulin or transcortin (75%)
Albumin (15%)
Pregnancy is associated with an increase in which cortisol binding protein?
CBG
What does an increase in CBG during pregnancy correspond to?
An increase in the amount of cortisol in the blood to maintain the free amount
How are glucocorticoids metabolised?
Steroid hormones are not water soluble
They are metabolised by the liver - glucuronidated to form water soluble forms that can be excreted in the urine
What other hormones are also bound to CBG and albumin?
Other glucocorticoids and progesterone
How are progesterone and cortisol metabolised?
Hepatic metabolism allows them to be rapidly excreted
How do glucocorticoids produce their effects?
By acting on intracellular glucocorticoid receptors and alterations in gene expression
This results in a delay in the order of hours/days
When are the effects of cortisol rapid?
In the feedback inhibition of ACTH secretion
At physiological concentrations, the most important actions of cortisol are on what?
Carbohydrate metabolism
How does the effects of cortisol oppose those of insulin?
Antagonise the effect of insulin on cellular uptake of glucose
Stimulates glycogenolysis
Stimulates hepatic gluconeogenesis
What are the effects of cortisol on growth hormone and catecholamines?
Cortisol potentiates the effects of growth hormone and catecholamines therefore stimulating lipolysis and mobilisation of fatty acids
What does cortisol cause in excessive concentrations?
Fat deposition in the face, trunk and intrascapular region of the shoulder
What are the effects of cortisol on the liver?
Cortisol stimulates amino acid uptake and therefore enhanced gluconeogenesis
What are the effects of cortisol in the periphery?
Inhibits amino acid uptake and protein synthesis leading to net loss of skeletal muscle and impeding growth
Glucocorticoids are able to stimulate aldosterone receptors. True or false
True
Name the enzyme possessed by aldosterone sensitive tissues that converts cortisol into inactive cortisone
11 beta hydroxysteroid dehydrogenase
When are there mineralocorticoids actions of glucocorticoids?
At very high concentrations of glucocorticoids
What is another effect of excess cortisol?
Enhanced vasoconstrictor responses to catecholamines resulting in raised blood pressure
What psychological effects can be produced by glucocorticoids?
Feelings of elation or sedation
At what times is there a rapid secretion of ACTH and cortisol?
at times of psychological and physiological stress e.g. trauma, infection or hypoglycaemia
What is the effect of glucocorticoids on the immune system?
- Inhibition of phospholipase A2
- Reduced synthesis of inflammatory mediators
- Suppression of the immune system
- Stop antibody production
What is the most important response of glucocorticoids
Response to stress
What happens in the absence of corticosteroids?
Death within 48 hours
What happens in a reduction in corticosteroids?
Inability to deal with certain stressful conditions e.g. cold mornings
Why might it appear that steroids are acting contrary to the individual’s best interests?
because they mask the damage
Suppress the inflammatory and immune responses that allow wound healing and tissue repair to occur
What do steroids allow you to do?
removes pain, lack of awareness of severity of the situation i.e. function despite the presence of illness and or injury
What happens to the concentration of the corticosteroids once the individual is in a safe place?
The concentrations of corticosteroids go down
What are the two physiologically most important mineralocorticoids?
Aldosterone and 11-deoxycorticosterone
Which are more important? Glucocorticoids or mineralocorticoids?
Glucocorticoids
What role does ACTH play in secretion of aldosterone?
Secretion of aldosterone is relatively uninfluenced by ACTH secretion
ACTH secretion causes the initial conversion of cholesterol to pregenenolone
What is the major factor in the control of aldosterone secretion?
Renin-angiotensin-aldosterone system
e.g. when blood pressure drops - renin is secreted
What else stimulates secretion of aldosterone?
Trauma, anxiety, hyperkalaemia and hyponatraemia
What inhibits aldosterone secretions?
Atrial natriuretic peptide (ANP)
What percentage of aldosterone is protein bound within the circulation?
50%
How does aldosterone have its effects?
Aldosterone acts on intracellular receptors which cause expression of ion channels to allow sodium and potassium ions across the membrane
What are the effects of aldosterone?
Sodium reabsorption in the distal tubule of the kidney in exchange for potassium ions or hydrogen ions
Where does aldosterone have its lesser effects?
In the ascending loop of Henley, proximal tubule and collecting duct as well as the colon, sweat and salivary glands
How does controlling sodium reabsorption influence water reabsorption?
Aldosterone causes sodium ion reabsorption –> increased sodium ion concentration –> causing water reabsorption in the collecting duct via ADH secretion
What effect does the interaction of the renin-angiotensin system, aldosterone and ADH have on the body?
Controls blood volume and therefore influences blood pressure
What are the pharmacological uses of glucocorticoids?
Replacement therapy
Immunosuppressive or anti-inflammatory effects in conditions e.g. arthritis, asthma/allergies/ treatment of proliferative conditions e.g. leukaemia
What are the pharmacological uses of mineralocorticoids?
Only for replacement therapy
What is used instead of aldosterone for replacement therapy and why?
Fludrocortisol because the short plasma half- life of aldosterone renders it unsuitable
Are glucocorticoids orally active?
Most glucocorticoids are orally active
Are glucocorticoids absorbed through the skin
This varies as does plasma half-life
What are the adverse effects associated with use of glucocorticoids
Suppression of wound healing Exacerbation of infections Inhibition of growth in children Osteoporosis in adults Development of diabetes mellitus Development of Cushing's syndrome
What does chronic administration of exogenous glucocorticoids result in?
Suppression of ACTH secretion leading to atrophy of the adrenal cortex
If steroid therapy is stopped suddenly, what can happen?
The adrenal cortex is unable to secrete endogenous corticosteroids and the patient suffers an Addisonian crisis
What is an Addisonian crisis?
Hyperactivity of adrenal gland - not able to produce the hormones needed & unable to respond to stress –> fatal
What is the disadvantage of anti-inflammatory corticosteroids?
They hide the symptoms but do not treat the underlying problem which may worsen
What is hydrocortisone? How does it act
A natural glucocorticoid secreted from the adrenal cortex.
It acts via intracellular glucocorticoid receptors to influence gene expression
What is hydrocortisone used for?
Hormone replacement therapy
Anti-inflammatory agent
Immunosuppressant
What are the adverse effects of hydrocortisone?
Hyperglycaemia
Osteoporosis
Cushing’s syndrome
